Drug Database: Tenofovir-Based Microbicides

What are tenofovir-based microbicides? What are tenofovir-based microbicides?

What are tenofovir-based microbicides?

Tenofovir-based topical microbicides are investigational products that are being studied to prevent sexual transmission of HIV.^3-10

Tenofovir, the HIV drug used in tenofovir-based microbicides, belongs to a class of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs).¹¹ NRTIs block an HIV enzyme called reverse transcriptase. By blocking reverse transcriptase, NRTIs prevent HIV from multiplying and from spreading to other cells.

To learn about how investigational drugs are tested during clinical trials, read the HIVinfo What is an Investigational HIV Drug? and HIV and AIDS Clinical Trials fact sheets.

How do topical HIV microbicides work? How do topical HIV microbicides work?

How do topical HIV microbicides work?

Topical HIV microbicides come in many different forms, such as gels, creams, films, vaginal rings (also called intravaginal rings or IVRs), and enemas. These products are designed to prevent HIV during sex, so they are used close to where HIV might enter the body during sexual activities – either the vagina or rectum.^11,12

Researchers have studied several different tenofovir-based microbicide products, including products for vaginal use (gel, film, tablet, intravaginal ring, and insert), as well as products for rectal use (gel, douche, and insert).^3–7,13-16 The tenofovir vaginal gel was the furthest along in development, but it failed to protect women from getting HIV in a Phase 3 trial.^3,17 Currently, the tenofovir rectal douche, tenofovir rectal gel, and intravaginal rings containing tenofovir are the most advanced products in Phase 2 developement.^4,7,8

Select clinical trials of tenofovir-based microbicides Select clinical trials of tenofovir-based microbicides

Select clinical trials of tenofovir-based microbicides

Tenofovir-based microbicides for rectal use

Rectal gel

Study Names: MTN-017; NCT01687218

Phase: 2
Status: This study has been completed.
Locations: United States, Peru, Puerto Rico, South Africa, and Thailand
Purpose: The purpose of this study was to look at whether a tenofovir rectal gel (used either once daily or before and after sex [intermittently]) is safe and acceptable in males without HIV. Researchers compared the tenofovir rectal gel to daily oral Truvada.⁴
Selected Study Results: Results were published in Clin Infect Dis (2017) and showed that tenofovir rectal gel was safe. Adherence was similar for both the gel used intermittently and oral Truvada but was lower for the gel used daily. In terms of acceptability, participants liked oral Truvada significantly more than either of the rectal gel regimens. When looking at how easy the products were to use and how likely the products would be used in the future, there was no significant difference between the gel used intermittently and oral Truvada.¹⁸
Additional Published Material:

• AIDS Behav article, 2017: Preference of oral tenofovir disoproxil fumarate/emtricitabine versus rectal tenofovir reduced-glycerin 1% gel regimens for HIV prevention among cisgender men and transgender women who engage in receptive anal intercourse with men
• PLoS One article, 2017: High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure Prophylaxis (PrEP) achieved in MTN-017 among men who have sex with men (MSM) and transgender women

Additional studies looking at the rectal use of tenofovir gel have been completed. Some of these studies are described below.

• MTN-007 (NCT01232803) was a Phase 1 study that looked at whether a tenofovir gel applied rectally is safe and acceptable.¹⁹ Results are available from PLoS One (2013).
• CHARM-01 (NCT01575405) and CHARM-02 (NCT01575418) were Phase 1 studies that looked at whether different formulations of tenofovir gel applied rectally were safe and acceptable.^20,21 Results are available from PLoS One (2015) and AIDS Res Hum Retroviruses (2015).

Rectal douche/enema

Study Names: HPTN 106; NCT06560684

Phase: 2
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to evaluate a tenofovir rectal douche compared to oral Truvada in men without HIV. Researchers looked at 1) how the body handles the tenofovir rectal douche, 2) what the tenofovir rectal douche does to the body, and 3) whether the tenofovir rectal douche is safe and acceptable.⁸

Additional studies evaluating tenofovir rectal douches or enemas have been completed, including the trials described below.

• DREAM-01 (NCT02750540) was a Phase 1 study that looked at whether different formulations of tenofovir rectal douches were safe and acceptable. Results are available from the J Infect Dis (2024) and Sex Transm Infect (2025).²²
• DREAM-02 (NCT04195776) was a Phase 1 study that looked at the timing of when a tenofovir rectal douche is used (before or after sexual activity) and how this affects the distribution (spread) of the douche solution and HIV in seminal fluid in the body. Results are available from J Infect Dis (2025).¹³
• DREAM-03 (NCT04016233) was a Phase 1 study that evaluated the use of multiple tenofovir rectal douches with and without non-medicated (water) douches given in different sequences. Results were presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2024).¹⁴
• ATN DREAM (NCT04686279) was a Phase 1 study that looked at whether a single dose of a tenofovir rectal douche is safe and acceptable. Results are available from the J Infect Dis (2025) and AIDS Behav (2025).²³
• DREAM-04 was a study that evaluated whether tenofovir douches prepared from packets of powder are acceptable and easy to use. Results are available from the J Acquir Immune Defic Syndr (2025).²⁴

Other rectal dosage forms

Rectal inserts containing tenofovir alafenamide/elvitegravir have also been studied. Two Phase 1 trials (RITE study; NCT06274398 and MTN-039; NCT04047420) have been completed. Results to MTN-039 are available from J Infect Dis (2024) and CROI 2023.^10,16

Tenofovir-based vaginal microbicides

Intravaginal rings

Study Names: Protocol B17-144; NCT03762382

Phase: 2a
Status: This study has been completed.
Location: Kenya
Purpose: The main purpose of this study was to evaluate the safety of a multipurpose prevention technology IVR delivering both tenofovir and levonorgestrel and a tenofovir only IVR in women from Kenya.⁷
Selected Study Results: Results were published in Front Reprod Health (2023) and showed that both the tenofovir and levonorgestrel IVR and the tenofovir only IVR used continuously for 90 days were safe. No genital lesions (sores) were seen. Data from the study indicated that the multipurpose tenofovir/levonorgestrel IVR has the potential to prevent HIV, HSV-2, and unintended pregnancy.²⁵
Additional Published Material:

• Sci Rep article, 2022: Genital microbiota of women using a 90 day tenofovir or tenofovir and levonorgestrel intravaginal ring in a placebo controlled randomized safety trial in Kenya

Additional Phase 1 studies of IVRs containing tenofovir have been conducted, including the studies described below.

• MTN-038 (NCT03670355) was a study that looked at whether a tenofovir-containing IVR used over 90 days is safe. This study has been completed, and results are published in J Int AIDS Soc (2024).²⁶
• CONRAD A13-128 (NCT02235662) was a study that looked at the safety of a tenofovir/levonorgestrel IVR and a tenofovir-only IVR used over one month. This study has been completed, and results are available from PLoS One (2018).²⁷
• CONRAD A15-138 (NCT03279120) was a study that evaluated the safety of a tenofovir/levonorgestrel IVR used over 90 days. This study has been completed. Results are published in PLoS One (2022) and Front Cell Infect Microbiol (2022).²⁸
• NCT03255915 is a study evaluating the safety of an IVR containing both tenofovir disoproxil fumarate and emtricitabine (TDF-FTC pod-IVR). This study is ongoing, but not recruiting participants.²⁹

Other vaginal dosage forms

Other forms of tenofovir-based vaginal microbicides have been investigated in early-phase trials, including vaginal inserts containing tenofovir alafenamide and elvitegravir. Two Phase 1 trials (MATRIX-001; NCT06087913 and NCT03762772) have been completed. Results to the NCT03762772 study are available from Front Cell Infect Microbiol (2023).^9,15

For more details on the studies listed above, see the Health Professional version of this drug summary.

What side effects might tenofovir-based microbicides cause? What side effects might tenofovir-based microbicides cause?

What side effects might tenofovir-based microbicides cause?

One goal of HIV research is to identify safe new drugs that have fewer side effects. The following side effects were observed in some of the studies of tenofovir-based microbicides listed above.

MTN-017 (NCT01687218)

In this Phase 2 study that compared tenofovir rectal gel (used daily or intermittently) with oral Truvada, the gel was reported to be safe. Most side effects were mild or moderate in intensity. Rates of side effects (moderate intensity or higher) were similar for the tenofovir rectal gel groups and the oral Truvada group. Excluding rectal infections, the most common side effect (moderate intensity) with the daily rectal gel was diarrhea.¹⁸

Protocol B17-144 (NCT03762382)

In this Phase 2a trial evaluating the continuous use of a tenofovir/levonorgestrel IVR and a tenofovir-only for up to 90 days, the most common side effects that occurred were bacterial vaginosis (a bacterial infection in the vagina), headache, and respiratory tract infections. The only product-related side effects were mild or moderate changes in menstrual bleeding patterns, which were reported in 6 participants using the tenofovir/levonorgestrel IVR and 1 participant using the tenofovir-only IVR.²⁵

Because tenofovir-based microbicides are still being studied, information on possible side effects of the products is not complete. As testing of tenofovir-based microbicides continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying tenofovir-based microbicides? Where can I get more information about clinical trials studying tenofovir-based microbicides?

Where can I get more information about clinical trials studying tenofovir-based microbicides?

More information on research studies related to tenofovir-based microbicides is available from ClinicalTrials.gov. (The ClinicalTrials.gov search can be modified so that you can get results that better match your interests.)

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

References References

References

1. National Center for Biotechnology Information. PubChem compound summary for CID 464205, tenofovir. Accessed October 25, 2026
2. Abdool Karim SS, Baxter C, Abdool Karim Q. Advancing HIV prevention using tenofovir-based pre-exposure prophylaxis. Antivir Ther. 2022;27(2):13596535211067589. doi:10.1177/13596535211067589. Accessed October 25, 2026
3. CONRAD. A Phase III, multi-centre, randomized controlled trial to assess the safety and effectiveness of the vaginal microbicide 1% tenofovir gel in the prevention of human immunodeficiency virus type 1 infection in women, and to examine effects of the microbicide on the incidence of herpes simplex virus type 2 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 28, 2011. NLM Identifier: NCT01386294. Accessed October 25, 2026
4. CONRAD. A Phase 2 randomized sequence open label expanded safety and acceptability study of oral emtricitabine/tenofovir disoproxil fumarate tablet and rectally-applied tenofovir reduced-glycerin 1% gel. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 27, 2012. NLM Identifier: NCT01687218. Accessed October 25, 2026
5. CONRAD. A Phase I clinical trial assessing the safety, pharmacokinetics, pharmacodynamics, and disintegration time of vaginal tablets containing tenofovir and/or emtricitabine. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 17, 2012. NLM Identifier: NCT01694407. Accessed October 25, 2026
6. CONRAD. A Phase I trial to assess the safety of tenofovir gel and film formulations: FAME 04. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 5, 2013. NLM Identifier: NCT01989663. Accessed October 25, 2026
7. CONRAD. Phase IIa, 90-day safety, adherence, and acceptability study of intravaginal rings releasing tenofovir with and without levonorgestrel among women in Western Kenya. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 16, 2018. NLM Identifier: NCT03762382. Accessed October 25, 2026
8. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 2 crossover study of on-demand PrEP formulations comparing rectal and oral tenofovir-based PrEP evaluating extended safety, acceptability, and pharmacokinetics/pharmacodynamics. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 2, 2024. NLM Identifier: NCT06560684. Accessed October 25, 2026
9. Eastern Virginia Medical School. A Phase I randomized, placebo-controlled, double-blind study to assess safety, pharmacokinetics, and modeled pharmacodynamics of a vaginal insert containing tenofovir alafenamide and elvitegravir. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 7, 2023. NLM Identifier: NCT06087913. Accessed October 25, 2026
10. Eastern Virginia Medical School. A double-blind, placebo-controlled, randomized Phase 1 study to evaluate the safety and pharmacokinetics of rectally administered tenofovir alafenamide/elvitegravir inserts. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 31, 2024. NLM Identifier: NCT06274398. Accessed October 25, 2026
11. Shattock RJ, Rosenberg Z. Microbicides: topical prevention against HIV. Cold Spring Harb Perspect Med. 2012;2(2):a007385. Accessed October 25, 2026
12. National Institute of Allergy and Infectious Diseases (NIAID). Microbicides to block transmission of HIV. Accessed October 25, 2026
13. Johns Hopkins University. A Phase 1 open label study evaluating the distribution of a tenofovir douche in combination with tap water douching and simulated receptive anal intercourse (DREAM-02). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 10, 2019. NLM Identifier: NCT04195776. Accessed October 25, 2026
14. Johns Hopkins University. A Phase I, open-label multiple dose safety, pharmacokinetic, pharmacodynamic, and acceptability study of tenofovir rectal douche. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 9, 2019. NLM Identifier: NCT04016233. Accessed October 25, 2026
15. CONRAD. A Phase I study to assess safety, pharmacokinetics, and pharmacodynamics of a vaginal insert containing tenofovir alafenamide and elvitegravir. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 16, 2018. NLM Identifier: NCT03762772. Accessed October 25, 2026
16. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 1 open label safety and pharmacokinetic study of rectal administration of a tenofovir alafenamide/elvitegravir insert at two dose levels. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 5, 2019. NLM Identifier: NCT04047420. Accessed October 25, 2026
17. Delany-Moretlwe S, Lombard C, Baron D, et al. Tenofovir 1% vaginal gel for prevention of HIV-1 infection in women in South Africa (FACTS-001): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2018;18(11):1241-1250. doi:10.1016/S1473-3099(18)30428-6. Accessed October 25, 2026
18. Cranston RD, Lama JR, Richardson BA, et al. MTN-017: a rectal Phase 2 extended safety and acceptability study of tenofovir reduced-glycerin 1% gel. Clin Infect Dis. 2017;64(5):614-620. doi:10.1093/cid/ciw832. Accessed October 25, 2026
19. CONRAD. A Phase 1 randomized, double-blinded, placebo-controlled rectal safety and acceptability study of tenofovir 1% gel. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 1, 2010. NLM Identifier: NCT01232803. Accessed October 25, 2026
20. Ian McGowan. A randomized, double blind Phase 1 safety, acceptability, and pharmacokinetic study comparing three formulations of tenofovir 1% gel administered rectally to HIV-1 seronegative adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 29, 2012. NLM Identifier: NCT01575405. Accessed October 25, 2026
21. Ian McGowan. An exploratory, double-blinded, randomized, pharmacokinetic and safety study of three rectally-applied tenofovir 1% microbicide gel formulations. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 1, 2012. NLM Identifier: NCT01575418. Accessed October 25, 2026
22. Johns Hopkins University. DREAM-01: optimization of a tenofovir enema for HIV prevention. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 11, 2016. NLM Identifier: NCT02750540. Accessed October 25, 2026
23. University of Pennsylvania. Safety, PK/PD, acceptability, and desirability of a novel HIV prevention douche among adolescent men (DREAM). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 22, 2020. NLM Identifier: NCT04686279. Accessed October 25, 2026
24. Diniz CP, Abdul-Massih S, Bagia C, et al. Rectal douche as HIV pre-exposure prophylaxis for receptive anal intercourse: an end user tenofovir powder sachet preparation feasibility study (DREAM-04). J Acquir Immune Defic Syndr 1999. 2025;99(1):75-80. doi:10.1097/QAI.0000000000003608. Accessed October 25, 2026
25. Mugo NR, Mudhune V, Heffron R, et al. Randomized controlled phase IIa clinical trial of safety, pharmacokinetics and pharmacodynamics of tenofovir and tenofovir plus levonorgestrel releasing intravaginal rings used by women in Kenya. Front Reprod Health. 2023;5:1118030. doi:10.3389/frph.2023.1118030. Accessed October 25, 2026
26. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 1, randomized pharmacokinetic and safety study of a 90 Day intravaginal ring containing tenofovir. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 12, 2018. NLM Identifier: NCT03670355. Accessed October 25, 2026
27. CONRAD. Phase I one-month safety, pharmacokinetic, pharmacodynamic, and acceptability study of intravaginal rings releasing tenofovir and levonorgestrel or tenofovir alone. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 14, 2014. NLM Identifier: NCT02235662. Accessed October 25, 2026
28. CONRAD. Phase I, 90-Day safety, pharmacokinetic, and pharmacodynamic study of intravaginal rings releasing tenofovir and levonorgestrel. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 23, 2017. NLM Identifier: NCT03279120. Accessed October 25, 2026
29. Oak Crest Institute of Science. Randomized order, controlled, double blind, crossover early Phase 1 pilot study to assess safety and pharmacokinetics of a tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) releasing IVR over 28 days compared to placebo. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 26, 2017. NLM Identifier: NCT03255915. Accessed October 25, 2026